Description of the Prior Art
The preparation of a particular acid of formula I, 2-(4-trifluoro-methylphenylamino)-3-methylbutanoate, and ortho-substituted derivatives thereof has been described in U.S. Pat. No. 4,226,802 to R. J. Anderson and T. A. Baer. In the Anderson et al process 4-aminobenzotrifluoride, or the corresponding ortho-substituted compound, is reacted with the sodium bisulfite addition product of isobutyraldehyde in an aqueous reaction medium, at a temperature above room temperature, followed by addition of sodium cyanide or potassium cyanide in aqueous medium to form the desired nitrile. The nitrile, on treatment with hydrochloric acid or other strong acid and an alcohol such as methanol at an elevated temperature forms a mixture of ester and amide. The ester can then be converted into the acid, or salt thereof.
Although the process of Anderson et al can be used to prepare other acids of Formula I as well, it is not satisfactory for commercial preparation of the acids of Formula I for several reasons. For example, in the preparation of the nitrile intermediate, solvents are required and a low yield (about 44%) of the nitrile is produced. Work-up is required before proceeding to the next step. In the preparation of the ester intermediate from the nitrile, the reaction must be run at elevated temperatures and proceeds through the amide intermediate, giving a mixture of ester and amide intermediates, requiring the extra step of either separating these two intermediates by chromatography (with a resulting low yield of about 47% of the ester) or the ester and amide mixture can be heated at about 80.degree. C. for a prolonged period (about four days) to convert most of the remaining amide to ester. The latter procedure would not be suitable for compounds with certain aromatic substituents which would be degraded by the severe conditions. Overall yields for preparing ethyl 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoate by the Anderson et al process, for example, is only about 38.3 percent. In contrast, by the process of this invention yields as high as 74.4 percent of 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoate can be obtained.
U.S. Pat. No. 3,538,152 describes a procedure for preparing unsubstituted amino acid salts by reacting aniline, formaldehyde and hydrocyanic acid in an aqueous solution at an elevated temperature to form the nitrile. This is treated with an aqueous, alkaline solution at an elevated temperature, producing an amide intermediate which subsequently hydrolyzed directly to the salt. No ester intermediate is involved, and prolonged, severe conditions, which degrade a variety of aromatic substituents, are required to effect the amide hydrolysis.